Despite significant advances in diagnosis and therapy, infections and sepsis remain a major cause of morbidity and mortality throughout the world. Even with aggressive management, many patients with severe infections develop complications and some die. Sepsis claims more than 200,000 lives in the United States annually (Angus, D. C. & Wax, R. S. (2001) Crit Care Med 29, S109-16). An intense inflammatory response accompanies the early phase of sepsis with markedly increased plasma levels of pro-inflammatory cytokines (Riedemann, N. C., Guo, R. F. & Ward, P. A. (2003) Nat Med 29, 517-24), in addition to other biochemical abnormalities. Much concerted research has gone into attempts at inhibition of specific inflammatory mediators in hope of developing pharmacologic treatments for sepsis. Nevertheless, activated protein C (APC) is the only drug proven to reduce the mortality of severe sepsis with an absolute reduction of death by 6% (Bernard, G. R., Vincent, J. L., Laterre, P. F., LaRosa, S. P., Dhainaut, J. F., Lopez-Rodriguez, A., Steingrub, J. S., Garber, G. E., Helterbrand, J. D., Ely, E. W. & Fisher, C. J., Jr. (2001) N Engl J Med 344, 699-709).
The negative health effects of infections and sepsis provide a strong incentive to identify new treatments as well as improved tests and approaches to evaluate therapy of infections and sepsis.